Glioblastoma multiforme is the most common primary brain tumor in adults, accounting for the majority of 18,500 cases of primary brain tumors diagnosed each year in the U.S. It has a dismal prognosis with a 12- 15 month median survival despite multimodality treatment. Novel therapeutic agents are urgently needed. MV-CEA is a novel viral agent deriving from the Edmonton vaccine strain of measles virus. The virus has been engineered to produce CEA that serves as a trackable marker of viral gene expression and can be used for monitoring of viral therapy in vivo. In preclinical work we have demonstrated significant antitumor potential of the virus, both in vitro and in vivo against glioblastoma animal models while CEA levels in the serum represent a helpful correlate of viral gene expression. This proposal includes two novel concepts: use of an attenuated measles virus of the Edmonton vaccine lineage as an antitumor agent against recurrent glioblastoma multiforme and use of a novel tracking system that could significantly improve our ability to monitor virotherapy trials. Our hypothesis is that MV-CEA will be a safe and effective agent for treatment of recurrent glioblastoma multiforme. We also hypothesize that the detection of CEA in patient serum can serve as an effective means of following viral gene expression, which could allow dose optimization in future applications of this agent. Therefore, we propose to conduct a phase I trial of MV-CEA in patients with recurrent glioblastoma multiforme with the following objectives: a) to assess the safety of intratumoral and resection cavity administration of MV-CEA in patients with recurrent glioblastoma multiforme and to determine the maximum tolerated dose of MV-CEA in this setting; b) to characterize the profile of viral gene expression at each dose level as manifested by the serum CEA concentrations and to assess viremia, viral replication, and measles virus shedding and persistence; c) to determine humoral and cellular immune response to the injected virus and correlate it with toxicity, viremia, CEA levels, and response; and d) to assess in a preliminary fashion the antitumor activity of this approach. ? ? ?

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Clinical Oncology Study Section (CONC)
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Timmer, William C
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Mayo Clinic, Rochester
United States
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